Communication between cells is central and ubiquitous in the human body. Key players in these processes are extracellular carbohydrate moieties bound to specific substances, e.g. different membrane molecules, cytokines or pathogens. One important component of these carbohydrate moieties is sialic acid, a nine-carbon monosaccharide present in most human and animal tissues. The concentration of sialic acid is high in tissues with high rates of processing and interaction such as the brain. It is present in all human body fluids, of which its content is especially high in milk. Sialic acid can be synthesised by the body.
Sialic acid has gained much scientific focus the last two decades, see Wang, B. and Brand-Miller J., The role and potential of sialic acid in human nutrition, Eur J Clin Nutr 2003; 57:1351-1369, and Schnauer R., Achievements and challenges of sialic acid research, Glycoconjugate J 2000; 17:485-499. Its role in cell communication covers regulation of molecular interactions, e.g. in the communication between cells and infectious agents. It is a structural part of cell membrane molecules, such as gangliosides and glycoproteins.
The dietary aspects of the emerging knowledge on sialic acid function in the human body have also been studied. Sialic acid is a major part of human milk oligosaccharides, indicating a nutritional role. Furthermore, brain and saliva of breast fed infants were found to contain significantly more sialic acid than those of infants fed commercial formula containing only minute amounts of sialic acid, suggesting an effective absorption of this carbohydrate moiety (see Tram, T. H., et al., Sialic acid content of infant saliva: comparison of breast fed with formula fed infants, Arch Dis Childh 1997: 77:315-8, Wang, B., et al., A longitudinal study of salivary sialic acid in preterm infants: Comparison of human milk-fed versus formula-fed infants, J Pediatr 2001; 138:914-6 and Wang B., et al., Brain ganglioside and glycoprotein sialic acid in breastfed compared with formula-fed infants, Am J Clin Nutr 2003; 78:1024-9).
Sialic acid exists in several chemical forms in nature. In body tissues it is found as part of oligosaccharide chains bound to proteins or lipids with only little available as free sialic acid. In milk it is mainly bound to glycoproteins or free oligosaccharides. However, minor quantities are found as free or lipid bound sialic acid.
In human milk, the majority of sialic acid is bound to oligosaccharides. The concentration of oligosaccharides containing sialic acid vary greatly with lactation stage as well as individually. Several authors have measured the content in human full term milk, finding contents ranging from more than 1 g/L in the first week to around 90-450 mg/L in mature milk (see Martin-Sosa, S., et al., Distribution of Sialic Acids in the Milk of Spanish Mothers of Full Term Infants During Lactation, J Pediatr Gastroenterol Nutr 2004; 39:499-503, Carlson, S. E., N-Acetylneuraminic acid concentrations in human milk oligosaccharides and glycoproteins during lactation, Am J Clin Nutr 1985; 41:720-6, Martin-Sosa, S., et al., Sialyloligosacchardies in Human and Bovine Milk and in Infant Formulas: Variations with the Progression of Lactation, J Dairy Sci 2003; 86:52-59, and Wang, B., et al. Concentration and distribution of sialic acid in human milk and infant formulas, Am J Clin Nutr 2001; 74:510-5).
In contrast, the majority of sialic acid in bovine milk is bound to proteins. Bovine mature milk contains only little oligosaccharide bound sialic acid. In colostrums the content is around 230 mg/L, whereas it is 25-54 mg/L in mature bovine milk (see Martin, M. J., et al., Distribution of Bovine Milk Sialoglycoconjugates During Lactation, J Dairy Sci 2001; 84:995-1000, and Martin-Sosa, S., et al., Sialyloligosacchardies in Human and Bovine Milk and in infant Formulas: Variations with the Progression of Lactation, J Dairy Sci 2003; 86:52-59).
Bovine based infant and follow on formulas are produced from mature bovine milk and the content of oligosaccharide bound sialic acid in these products has been found to be 15-35 mg/L, whereas that of preterm formulas was found to be slightly higher with 80 mg/L. Soy formulas contain no oligosaccharide bound sialic acid. See Wang, B., et al. Concentration and distribution of sialic acid in human milk and infant formulas, Am J Clin Nutr 2001; 74:510-5 and Martin-Sosa, S., et al., Sialyloligosacchardies in Human and Bovine Milk and in Infant Formulas: Variations with the Progression of Lactation, J Dairy Sci 2003; 86:52-59.
With the sialyllactose concentrate of the present invention, infant formulas can be enriched with oligosaccharide bound sialic acid in concentrations matching human milk, i.e. the total concentration of oligosaccharide bound sialic acid can be increased to 100-1500 mg/L matching concentrations of human milk of various lactation stages. However, the scope of the present invention is not limited to this range of enrichment due to the great variations in human milk composition and also due to the fact that other food applications may require other oligosaccharide bound sialic acid concentrations.
Commercially, sialic acid containing ingredients for use in foods are available. One such ingredient is bovine sialic acid bound to the protein κ-casein, commercially available from Aria Foods (Denmark) among others. Synthetically produced sources of sialic acid also exist, e.g. synthetic sialyllactose from MoBiTech, Germany, as well as recombinant human κ-casein containing sialic acid (see U.S. Pat. No. 6,270,827).
Thus, existing commercially available products containing sialic acid are either not obtained from natural sources, i.e. they are produced synthetically or by using recombinant techniques, or they comprise sialic acid bound primarily to proteins and not oligosaccharides as in human milk. The product of the present invention is as far as we know the first product comprising a concentrate of oligosaccharides containing sialic acid which is derived from a natural ruminant milk source in a high concentration.